Definition
Bacteria are small, primarily microscopic, single-celled
organisms defined as members of the group prokaryotes, which lack internal membrane-enclosed organelles such as a nucleus.
Microbial classification has its roots, like those of more evolved organisms (such as plants and animals), in the system originally developed by Swedish botanist Carolus Linnaeus in the mid-eighteenth century; such systems reflect the evolutionary relationships among these organisms as largely confirmed in DNA (deoxyribonucleic acid) studies during the latter half of the twentieth century. Members of the same genus are considered closely related and may even interbreed. Members within the same order or family are not as closely related, yet they still reflect a common ancestry. An example is that of the class Mammalia, which includes both humans and whales. The lowest levels of the taxonomic hierarchy are the genus and species, with their Latinized binomial nomenclature considered the scientific name.
The system is applied to bacteria in an attempt to bring a sense of order in defining genetic relationships: Members of the same genus are considered closely related, while members of different genera are considered relatively unrelated. Variants within the same species are designated as subspecies or serovars, representing variations in surface molecules.
However, naming and classification of bacteria have often drawn on historical aspects of the organisms, such as the person who first isolated or characterized the bacterium (Theodor Escherich) or the disease (cholera). Members of different genera may actually be variants of the same species; the pathogens Shigella, the etiological agent of bacterial dysentery, and Escherichia, which is associated with a variety of gastrointestinal or urinary tract infections, are really variations of the same species. Among the reasons for the confusion in taxonomy is the instability of genetic material.
Bacteria have the ability to carry out horizontal transfer of genetic material:
Large segments of DNA readily pass or are exchanged not only among different
genera but also among different orders. In this manner, not only do the genetic
characteristics of bacteria change, but harmless organisms may acquire the ability
to cause disease. Despite these shortcomings of bacterial taxonomy, modern genetic
analysis has resulted in more accurate classification that reflects the
relationships among bacteria. Also, new names for genera as the underlying
molecular biology of microorganisms becomes better understood.
Bacteria are classified into two general categories, depending upon their cell-wall structure: gram-positives, which have a wall predominately composed of peptidoglycan (polysaccharide and protein), and gram-negatives, which have a cell wall composed primarily of lipopolysaccharide (lipids and polysaccharides). Gram-positives include members of the phylum Firmicutes, while gram-negatives represent most of the rest. The gram “characteristic” is named for Hans Christian Gram, a nineteenth and twentieth century German scientist.
Natural Habitat and Features Organisms that are etiological agents of disease generally associate with the
host in two ways: as members of the normal flora, or microbiota, or as pathogens that must enter the body
through “openings” such as respiratory passages (the nose or mouth), the
gastrointestinal tract, or the genitourinary tract.
Resident pathogenic bacteria survive in the host primarily within niches that allow their survival. For example, the skin provides both a natural barrier to sterile regions within the body and a surface environment inhibitory to many types of microorganisms. The secretion of fatty acids in sebum creates an environment of low pH (acidity), and the secretion of NaCl (sodium chloride, or salt) in body sweat creates an environment of high salt. Organisms that become part of the microbiota on the skin, primarily members of the staphylococci and certain streptococci, must be able to survive under these conditions.
The microbiota of the colon consists of large numbers of primarily anaerobic, nonpathogenic bacteria, with an estimate of about one thousand bacteria in one gram of feces. Competition from the resident flora is generally sufficient to prevent transient pathogens from becoming established. In turn, anything that disrupts the resident flora can allow pathogens to become established. For example, the use of broad-spectrum antibiotics may remove the normal bacteria in the colon. Clostridium difficile, commonly present in a dormant spore state in the colon, can establish itself under these conditions and produce toxins that result in severe ulcerative colitis.
To carry out infection, pathogenic bacteria must exhibit characteristics
that not only allow transmission between hosts but also allow them to survive and
colonize within the new host. Such features are referred to as virulence factors, and they represent whatever means bacteria use to resist
the host defenses and to produce the symptoms of disease. The most obvious
examples are those of toxins, which are placed in two general categories: endotoxins, pharmacologically active chemicals that compose a portion of the
lipid component of the cell-wall structure of gram-negative bacteria, and exotoxins, which are secreted by some, primarily gram-positive, bacteria.
Other virulence factors include a polysaccharide or protein capsule that surrounds
some bacteria and prevents destruction by white blood cells (phagocytes) of the
host’s immune system, and fimbriae, hairlike structures on the cell surface that
allow attachment and colonization in the host.
Pathogenicity and Clinical Significance The transmission of bacteria varies significantly and depends upon the
environmental niche of the organism in the host. Respiratory infections such as
whooping
cough or tuberculosis are transmitted through
respiratory secretions, such as droplets resulting from sneezes or coughs, which
are inhaled by the recipient. Sexually transmitted diseases such as
gonorrhea or syphilis are passed through sexual
contact. Some illnesses, such as staphylococcal infections, may be
transmitted by direct contact or by ingestion of contaminated foods.
Staphylococci. Members of the family Staphylococcaceae, a group of gram-positive cocci, include some of the most common pathogenic organisms that also can produce some of the most deadly infections. There are more than forty species of Staphylococcus, most of which are harmless. The two species of clinical importance are S. epidermidis, a member of the skin microbiota, and S. aureus, commonly found on the skin and nasal passages.
The staphylococci are differentiated from the streptococci, which they
physically resemble, by their ability to produce catalase, an enzyme that, when
mixed with peroxide, produces bubbles of oxygen. S. aureus in
particular has the ability to be a significant pathogen because of the large
variety of toxins various strains may produce. Most strains of S.
aureus produce several forms of coagulase, an enzyme that causes serum
to clot and that may play a role in the formation of boils. In addition, various
strains may produce enzymes that lyse red blood cells (β-hemolysins), may produce
white blood cells (leukocidins), and may induce severe shock (toxic shock syndrome
toxin). The experience with which most persons encounter the staphylococci is in
the form of what is commonly known as food poisoning, the result of exposure
to a heat-stable staphylococcal enterotoxin.
Streptococci. The streptococci are gram-positive cocci that physically resemble the staphylococci, but are genetically different and are differentiated from the latter by their lack of production of catalase. The streptococci is a large and diverse collection of species that were originally classified into groups by Rebecca Craighill Lancefield in the 1930’s on the basis of surface carbohydrates; the Lancefield classification scheme is still used.
Group
A, which includes Streptococcus pyogenes (“pus-creator”), is the
most important of the streptococci. Most commonly associated with strep throat,
infection with S. pyogenes can potentially lead to
rheumatic
fever or glomerulonephritis. S. pyogenes can
produce a variety of toxins, any of which may contribute to virulence. Such toxins
include enzymes that can lyse red blood cells (streptolysins) and can cause
impetigo, erythrogenic toxins (scarlet
fever), and severe shock (toxic shock syndrome toxin). Other
species of streptococci may contribute to the formation of dental carries
(S. mutans) and to meningitis in infants (group B S.
agalactiae). S. pneumoniae is a common cause of
bacterial pneumonia, and before the discovery of antibiotics,
it was associated with a high proportion of deaths in the elderly.
Enteric bacteria. The family Enterobacteriaceae, more commonly
called the enteric bacteria, is a diverse group of gram-negative bacteria that are part of the
microbiota of the intestinal tract in both warm-blooded and cold-blooded
organisms. Not all are pathogens, however. Most provide a benefit to the host by
suppressing the colonization of pathogens while at the same time producing B and K
vitamins for that host.
The species perhaps best known to the general public is Escherichia coli. Most types of E. coli are harmless. However, some types or strains have acquired the ability to invade host intestinal cells or to produce a variety of enterotoxins associated with food poisoning.
E. coli infections are routinely classified on the basis of the
type of disease and are placed in the following five categories: enterotoxigenic,
which causes the illness commonly referred to as travelers’
diarrhea, the result of two forms of toxins produced by this
strain, one of which is nearly identical to that associated with cholera;
shiga-toxin-producing, which produces a toxin that likely originated with
Shigella, the cause of bacterial dysentery (the most noted
strain is E. coli O157:H7, which produces a potentially
life-threatening hemolytic anemia); enteropathogenic, which is a cause of
severe diarrhea in infants; enteroinvasive, which is capable of invading
intestinal cells; and enteroaggregative, which is associated with chronic diarrhea
in persons in developing countries.
Salmonella and Shigella are the two other major
pathogens among the enterics. Salmonella
is a common contaminant of cold-blooded animals, birds, and
ruminants such as cattle and sheep. The most common result of infection in humans
is severe enterocolitis, usually the result of fecal contamination of
food or water. Historically S. typhi was the etiological agent of
typhoid
fever, a significant cause of mortality in cities in which
sewage was untreated. Shigella is the cause of bacterial
dysentery, a disease also transmitted through contaminated food or water.
Another enteric, Yersinia pestis
, is the agent of bubonic plague, a major killer between
the fourteenth and nineteenth centuries. Plague is endemic to many rodents and is
transmitted to humans through the bite of a flea.
Clostridia. The clostridia are gram-positive rods that form spores, allowing them to survive in the soil or as part of the intestinal microbiota. While most are nonpathogenic, helping to degrade organic material, several are important pathogens because of the toxins they encode. The diseases they cause are in part the result of their being strictly anaerobic (oxygen free).
C. tetani spores are ubiquitous. If they enter a cut or wound, or
any anaerobic environment, the spores may germinate, producing a toxin associated
with tetanus. If the infected person has not been immunized
against the toxin, the disease produces a loss of control of motor neurons,
resulting in a spastic paralysis (lockjaw). Botulinum toxin, produced by
C. botulinum, is among the most potent toxins known. While
rare, botulism poisoning usually results from canned vegetables
that have not been properly sterilized.
Campylobacter and Helicobacter, members of the ε-Proteobacteria, are among the most recently discovered pathogens. Campylobacter
is an important cause of infant diarrhea, particularly in developing countries. Helicobacter
infections of the stomach were found to be associated with the development of stomach ulcers. As a result of this connection, the treatment of ulcers with antibiotics rather than with palliative methods (antacids) was found to be more effective in preventing ulcer recurrence.
Drug Susceptibility Toxic substances such as mercury, which could be used to treat diseases such as syphilis, have been known since the seventeenth century. However, the concept of a “magic bullet,” a safe antimicrobial agent that would kill germs and cure disease, dates to the 1880’s, when the germ theory of disease was evolving. The first success in this area of research was the arsenic compound salvarsan, developed by German physician Paul Ehrlich, who was able to successfully treat syphilis with the compound. However, this also was too toxic for general use. Arguably, the primary impetus in researching antimicrobial drugs grew from the enormous number of casualties of World War I, in which infection was as likely to result in death as was the wound itself.
The first success in antimicrobial therapy was the discovery of sulfa drugs by German physician Gerhard Domagk. Working closely with the dye industry in the 1920’s and 1930’s,
Domagk discovered that sulfur derivatives, the sulfonamides, could kill
streptococci, among the deadliest of bacteria. German
dictator Adolf Hitler and the Nazi Party limited research to finding ways to
improve the effectiveness of the drugs, and it was not until after World War II
that the full potential of sulfa drugs was seen. Meanwhile,
penicillin, discovered by British scientist Alexander
Fleming in 1928, became the first broad-spectrum antibiotic effective against most
major bacteria.
Antimicrobials fall into four general categories: analogs such as the sulfa drugs, which block DNA replication; inhibitors of cell-wall synthesis, such as the penicillins, cephalosporins, and vancomycin; inhibitors of cell-membrane function, such as polymyxin; and inhibitors of bacterial protein synthesis, such as tetracycline, chloramphenicol, streptomycin, and erythromycin.
Bacteria have evolved a variety of means to resist antibiotic functions. In some cases, resistance is a natural function of bacterial structure. For example, the penicillins inhibit cross-linking of the cell-wall peptidoglycan in gram-positive cells such as the staphylococci and streptococci. Because most gram-negative bacteria such as E. coli and Salmonella have cell-wall structures containing limited amounts of peptidoglycan, historically they were more resistant. Some bacteria have acquired genetic information to produce enzymes that destroy or inactivate antibiotics. In particular, most staphylococci have developed a penicillinase that inactivates penicillin, rendering the drug useless. Other bacteria have acquired genetic information to enzymatically modify other antibiotics. Bacteria may also become resistant by changing the target of the drug; altered ribosome structures confer resistance to erythromycin or streptomycin. Likewise, bacteria may acquire mechanisms to pump the antibiotic out of the cell.
Bibliography
Brooks, George, et al. Jawetz, Melnick, and Adelberg’s Medical Microbiology. 25th ed. New York: McGraw-Hill, 2010. A medical text that summarizes the major groups of pathogens, with concise descriptions of virulence factors associated with disease.
Hager, Thomas. The Demon Under the Microscope. New York: Harmony Books, 2006. Story behind the first “miracle drug,” the sulfa drugs that were effective in treating streptococcal infections. Largely a biography of Gerhard Domagk, their discoverer, the story also delves into antibiotic research and the politics and economics behind the work.
Koch, Arthur L. The Bacteria: Their Origin, Structure, Function, and Antibiosis. Bloomington, Ind.: Springer, 2006. Evolutionary history of bacteria. Focuses on how the evolution of the cell-wall structure led to the diversification of bacterial species.
Murray, Patrick, et al., eds. Manual of Clinical Microbiology. 9th ed. Washington, D.C.: ASM Press, 2007. Provides extensive coverage of pathogenic bacteria and mechanisms of disease. The detailed discussions are not for the casual science reader, but the book does serve as an excellent resource for the subject.
Singleton, Paul. Bacteria in Biology, Biotechnology, and Medicine. 6th ed. New York: John Wiley & Sons, 2004. A concise description of bacteria and their roles in nature. Included are chapters on bacterial structure, staining, and methods of classification and identification.
Willey, Joanne, et al. Prescott’s Microbiology. 8th ed. New York: McGraw-Hill, 2011. Outstanding textbook of microbiology. Specific chapters detail the most important organisms, including pathogens. The authors summarize pathogenic mechanisms in amanner that will not overwhelm readers.
